Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

Table 1 Pharmacologic strategies for targeting myeloid-derived suppressor cells inhibition

Function	Drug	Target pathway	Synergistic	Diseases	Ref.
Inhibition of MDSC recruitment	Bevacizumab			Non-small cell lung cancer	Koinis et al[91]
	IL-17			Breast cancer	Ma et al[98]
	flubendazole	STAT3		Melanoma	Li et al[96]
	CXCR2			Rhabdomyosarcoma	Highfill et al[99]
	IL-6	STAT3-DNMT		Colorectal cancer	Smith et al[97]
	G-CSF			Colorectal cancer	Li et al[107]
	Carnosic acid		Cisplatin	Lung cancer	Liu et al[101]
	CDDP and PEM			Mesothelioma	Otsuka et al[93]
	Dimethyl itaconate			Colorectal cancer	Wang et al[103]
	Embelin	C/EBPβ and STAT3		Colitis-associated cancer	Wu et al[95]
	LDK378	p38-GRK2-CCR2		Sepsis	Hu et al[105]
	Inhibition of YTHDF2			Autoimmune hepatitis	Lyu et al[106]
	Terbinafine			Colorectal cancer	Hu et al[102]
	Targeting of SLC25A22		Immunotherapeutic	KRAS-mutant colorectal cancer	Zhou et al[89]
	Sulforaphane and doxorubicin			Breast cancer	Rong et al[92]
	Polypeptide nanoformulation		Immunotherapeutic	Breast cancer and colon cancer	Feng et al[94]
	OSU-53	AMPK		Melanoma	Trikha et al[104]
	Curcumin			Lung cancer	Wang et al[100]
MDSC depletion	5-Fluorouracil	p53-Fas		Colorectal cancer	Yang et al[108]
	Docetaxel			Breast cancer	Kodumudi et al[109]
	Metformin			Colorectal cancer	Kang et al[110]
	Amino-biphosphonate	MMP-9		Breast cancer	Melani et al[117]
	Apt/PDGss@pMOF			Triple-negative breast cancer	Chen et al[115]
	Baicalein	Nrf2/HO-1		Lupus nephritis	Li et al[118]
	DS-8273a	TRAIL-R2		Pan-cancer	Dominguez et al[116]
	Histamine		Anti-PD-1/PD-L1	Pan-cancer	Grauers et al[114]
	Shugan Jianpi Formula			Breast cancer	Lu et al[119]
	OLT1177	NLRP3	Anti–PD-1	Melanoma	Tengesdal et al[120]
	Aptamer	IL4Rα		Breast cancer	Roth et al[121]
	Sunitinib	STAT5		Renal cell carcinoma	Ko et al[112]
	Lenalidomide		Cancer vaccine	Lymphomas	Sakamaki et al[111]
Inducting MDSC differentiation	ACEI			Colorectal Cancer	Bueno et al[112]
	Brequinar	DHODH	Anti–PD-1	Breast cancer	Colligan et al[123]
	Vitamins A, D3, and E			Head and neck cancer	Lathers et al[124]; Lee et al[125]
	Casein kinase 2		Anti-CTLA4	Pan-cancer	Hashimoto et al[126]
Inhibiting MDSC activity	Celecoxib	COX-2		Mesothelioma	Veltman et al[127]
	Entinostat	HDAC		HER2+ Breast Tumor	Sidiropoulos et al[128]
	Cimetidine			Lung tumor	Zheng et al[131]
	Compound39	potent GCN2 inhibitor		Renal carcinoma	Jackson et al[140]
	CTX014	Jagged1/2		Pan-cancer	Sierra et al[141]
	Asparagus polysaccharide			Colorectal Cancer	Zhang et al[135]
	Curcuma	TLR4-NF-κB		Pan-cancer	Jiang et al[134]
	Ibrutinib		Anti-PD-L1	Neuroblastoma	Ishfaq et al[129]
	IFN-α/β		Anti-PD-1	Colorectal cancer	Chen et al[132]
	TJ-M2010-5	Myd88		Colorectal cancer	Wang et al[136]
	Tivozanib	c-Kit/SCF		HCC	Kalathil et al[130]
	Sildenafil	Phosphodiesterase-5		Abdominal malignancies	Tai et al[70]
	IPI-145	PI3Kδ/γ	Anti-PD-L1	Head and neck cancers	Davis et al[138]
	Mitochondrial complex I inhibitors			Melanoma	AbuEid et al[139]
	MF-766		Anti-PD-1	Pan-cancer	Wang et al[137]
	Lipoprotein Nanoparticle			Lung carcinoma	Plebanek et al[142]

MDSC: Myeloid-derived suppressor cells; HCC: Hepatocellular carcinoma; PD-L1: Programmed cell death 1 ligand 1; PD-1: Programmed cell death protein 1.